br Additionally ischemic events were
Additionally, ischemic events were classified into early events (starting < 15 days) and delayed events (starting 15 days). Fifteen early ischemic events were reported, whereas 47 delayed ischemic events were reported in the current study. Within the early events, 12 events were reported among patients receiving bevacizumab-containing regimens, and 3 events were reported among patients receiving patients receiving nonebevacizumab-containing regimens. With additional univariate logistic regression analysis, bevacizumab-containing regimens were predictive of both early and delayed ischemic events (P ¼ .026 and P ¼ .002, respectively).
The current study provides an analysis of the patterns and pre-dictors of cardiac toxicities among patients with metastatic CRC receiving Actinomycin D number of different first-line 5-FU-based chemotherapy regimens. Generally, bevacizumab- and panitumumab-containing regimens seem to be associated with a higher risk of cardiac toxic-ities compared with other 5-FU-based regimens. More specifically,
Table 4 Multivariate Logistic Regression Analysis for Factors Predicting Arrhythmias
Parameters Odds Ratio (95% CI) P Value
Concurrent panitumumab treatment
Abbreviations: BMI ¼ body mass index; CI ¼ confidence interval; HR ¼ hazard ratio.
Table 5 Multivariate Logistic Regression Analysis for Factors Predicting Ischemic Episodes
Parameters Odds Ratio (95% CI) P Value
Concurrent bevacizumab treatment
Abbreviations: CI ¼ confidence interval; HR ¼ hazard ratio.
bevacizumab-containing regimens seem to increase the risk of 5FU-related ischemic events, whereas panitumumab-containing regimens seem to increase the risk of arrhythmias.
A number of pathologic mechanisms were hypothesized to explain the development of 5-FU cardiotoxicity. These include arterial endothelial damage, followed by platelet aggregation, arterial vasoconstriction, and myocardial inflammation.13 Bevacizumab (like many other antiangiogenic agents) is well-known to predispose to thromboembolic complications.14 Thus, the increased risk of ischemic events with bevacizumab-containing regimens is expected. Likewise, panitumumab is well-known to predispose to electrolyte disturbances (especially hypomagnesemia).15 This might partly explain the increased risk of cardiac arrhythmias with panitumumab-containing regimens.
The current study contains a number of limitations that have to be recognized. First, the issue of cardiac toxicity was not the primary research question of any of the included studies. Thus, although the current analysis is based on prospectively collected datasets, deoxyribonucleic acid (DNA) essen-tially represents a retrospective analysis of these prospectively collected datasets with all the expected shortcomings of a retrospective analysis. Second, because of the heterogeneity of data collection practices as well as the protocol of each study, some baseline information was missing. These limitations need to be weighed against the obvious strengths of the current analysis; most importantly, the reliance on well-controlled prospectively collected information, which would provide a higher credibility compared with previous reports of 5-FU-related cardiotoxicity. Moreover, because patients with a history of serious clinical illness (including cardiac events) were excluded from inclusion into these studies, the establishment of an association with treatment regimens seems to be more credible.
It has also to be noted that given the highly selective context of patients included within clinical trials (ie, younger age, good per-formance status, and minimal comorbidity), it is expected that rates and severity of cardiac toxicity would be quite higher in real-life settings compared with the findings of the current analysis. Thus, extra caution should be exercised when administering these regi-mens in routine practice settings.